Sacred Sones in Peru like at Saksaywaman or Machu Picchu and the misuse of these

"Keiner ist so verrückt, dass er nicht einen noch

Verrückteren fände, der ihn versteht."

Die Harzreise von Heinrich Heine

When you go to Saksaywaman or Machu Picchu you will find quite a lot of stones used at terrace walls or buildings, which attract even more eccentrics and esoteric people. They believe that the stones are emitting energy and that they can receive this energy. But if you look soberly and in a more scientific way at it: which kind of energy are the big boulders emitting? How can on measure this energy? Somehow I felt reminded of: “No one is so crazy that he doesn‘t find someone even more insane, who understands him.” Translated from the German text above. And no, it isn’t by Friedrich Nietzsche, it’s by Heinrich Heine, who has written this line in “Die Harzreise” – The Journey to the Harz.

Let’s have a couple of looks at this strange phenomenon. 

 

No go and touch any more!

 

Oh, we'll find another big stone.

 

Or we let the sourroundings replenish us with energy.

 

A harless big slab of stone?

 

Not so harmless - it leads to mass hysteria.

Progressing Autumn

The funeral pyre

Made of garbage and debris

But sparks hit the night

Slow moon’s arising

Leaves have already hit the ground

Last cricket has died

The sun has hidden

Yesterday’s pale afterglow

Crickets have gone, too

Wind moving

Curled leaves

Like hurrying mice

 

Some haiku in German:

Nebel in Bäumen

Umgeben von Dunkelheit

Tropfen auf Blättern

Ilex vor Ziegeln

Grau gefärbt vom November

Lachen der Kinder

Duft von frischem Holz

Der DachFirst ist errichtet

Leere Fenster noch

Die Kronen entlaubt

„Und aus den Wiesen steiget ...“

Mondlicht auf Allem

BI 655064, an Antagonistic Anti-CD40 Antibody, in the Treatment of Rheumatoid Arthritis at the 2016 Annual Meetings of EULAR and ACR

I have been interested in CD-40 for a couple of years now. Boehringer Ingelheim has developed a CD40 antigen inhibitor, BI 655064. Boehringer Ingelheim has terminated a phase I trial for immune thrombocytopenic purpura in the US this September. Adisinsight didn’t show any new reports on phase 1 studies in rheumatoid arthritis, which is strange as there had been two abstracts at the EULAR 2016 Annual Meeting in London and one abstract at the ACR 2016 Annual Meeting in Washington, which concluded just a couple of days ago.

S. Visvanathan and collegues presented at the EULAR 2016 [FRI0231]:“Treatment with BI 655064 (antagonistic anti-CD40 antibody) modulates biomarkers associated with Rheumatoid arthritis (RA)”. In conclusions we read: These results demonstrate that treatment of RA patients with BI 655064 decreases activated B cell subsets, inhibits the production of pathogenic autoantibodies, and reduces the level of circulaiting inflammatory and bone resorption biomarkers at 12 wks  [weeks].”

S. Daniluk and collegues presented at the EULAR 2016 [SAT0147]: “Safety and efficacy of BI 655064, an antagonistic Anti-CD40 antibody in rheumatoid arthritis (RA) patients”. In conclusions the authors tell us: “In this relatively small proof-of-clinical-concept trial, treatment of

MTX IR RA patients with BI 655064 did not indicate a relevant safety concern and showed moderate efficacy, which might have been impacted by the relatively high placebo response rate and the imbalance in baseline CRP.”

S. Visvanathan and collegues presented at the ACR 2016 [1588]: “Treatment with BI 655064 (Antagonistic Anti-CD40 Antibody) Modulates Clinical and Biomarker Parameters Associated with Rheumatoid Arthritis (RA)”.In conclusion we read: “Treatment of MTX-IR RA [methotrexate inadequate responders rheumatoid arthritis] patients with BI 655064 resulted in moderate efficacy, […]. Treatment with BI 655064 decreased selected activated B cell subsets, inhibited RF [rheumatoid factor] production, and reduced levels of select circulating inflammatory and

bone resorption biomarkers through 12 wks [weeks] in RA patients.”

The studies show moderate efficacy in rheumatoid arthritis patients with inadequate response to MTX and a reduction of circulating inflammatory and bone resorption biomarkers, which might be a hint at the possibility to reduce or stop radiographic progression. Half a year ago AbbVie and Boehringer Ingelheim announced sharing responsibility for future clinical development. “AbbVie gains rights to an anti-CD-40 antibody, BI 655064, currently in Phase 1 development. [March 2016]”.  Hopefully, a phase 2 study is initiated soon.

Links:

http://rheumatologe.blogspot.de/2012/08/targeting-cd-40-preliminaries-at-eular.html

http://adisinsight.springer.com/drugs/800035513

S. Visvanathan, M. Ramanujam, C. Schoelch, R. Vinisko,U. Mueller-Ladner, S. Padula, J.S. Fine, J. Steffgen: FRI0231 / TREATMENT WITH BI 655064 (ANTAGONISTIC ANTI-CD40 ANTIBODY) MODULATES BIOMARKERS ASSOCIATED WITH RHEUMATOID ARTHRITIS (RA). DOI: 10.1136/annrheumdis-2016-eular.2051

S. Daniluk, R. Ptaszynski, U. Mueller-Ladner, A. Petrikova, H. Kellner, E. Dokoupilova, B. Kwiatkowska, R. Alten, C. Schwabe, B. Rosenstock, T. Doan11, R. Thiedmann , F. Fleischer, J. Hilbert, S. Visvanathan, S. Padula, J. Steffgen: SAT0147 / SAFETY AND EFFICACY OF BI 655064, AN ANTAGONISTIC ANTI-CD40 ANTIBODY IN RHEUMATOID ARTHRITIS (RA) PATIENTS. DOI: 10.1136/annrheumdis-2016-eular.1271

Sudha Visvanathan, Meera Ramanujam, Corinna Schoelch, Patrick Baum, Richard Vinisko, Ralf Thiedmann, Ulf Müller-Ladner, Stefan Daniluk, Rafal Ptaszyński, Steven Padula, Jay S. Fine and Jürgen Steffgen [1588]: “Treatment with BI 655064 (Antagonistic Anti-CD40 Antibody) Modulates Clinical and Biomarker Parameters Associated with Rheumatoid Arthritis (RA)”. http://acrabstracts.org/abstract/treatment-with-bi-655064-antagonistic-anti-cd40-antibody-modulates-clinical-and-biomarker-parameters-associated-with-rheumatoid-arthritis-ra

AbbVie and Boehringer Ingelheim announce global collaboration on promising immunology compounds  https://www.boehringer-ingelheim.com/press-release/abbvie-boehringer-ingelheim-immunology-compounds

 

 

...

Otezla® and an increased risk of suicide

Otezla® (active ingredient: Apremilast from Celgene) has been given a "Red Hand Letter" this month. In a "red hand letter" all physicians in Germany get important communications about a drug (e.g. new discovered side effects of a drug).

In the summary the letter reads: "Occasional cases of suicidal thoughts and suicidal behavior (with or without history of depression) have been reported in clinical trials and after market introduction (frequency ≥1/1,000 to ≤1/100). Cases of successful suicide have been reported after market introduction in patients treated with Apremilast."

The following background information has been given: "Notes on suicide thoughts and suicide behaviors: - The data collected after market launch by 20^th March 2016 included 65 reported cases with 5 suicides completed, 4 suicide trials, 50 cases with suicide thoughts, 5 cases with depression and suicide thoughts, and 1 case with suicidal behavior. (...)"

Perhaps I’m too skeptical about small molecules, but I had argued already years ago that a change in communication within the cell could lead to more problems in regard to side effects than the interruption of communication between cells (e.g. by biologics). For the biologics used up to date in rheumatology, I do not know an increase in suicide and suicidal ideation; however, Amgen had withdrawn from the development of brodalumab (anti-IL-17R autoantibody). Brodalumab will be available in the US as Siliq, an introduction to Europe is expected for the first quarter of 2017. More about this has been discussed in the psoriasis network (in German!). For Tofacitinib, two suicides were listed in 2012, "ADVISORY COMMITTEE MEETING TOFACITINIB FOR THE TREATMENT OF RHEUMATOID ARTHRITIS". For baricitinib the number of patients tested may still be too low to answer this question.

I have used Otezla® very rarely since I have preferred other drugs, which were approved earlier, because of better knowledge and more experience. I won’t change this attitude. On the other hand, a danger that is known is also a lesser danger. 

Links (some texts in German):
Psoriasis-Netz zu Brodalumab http://www.psoriasis-netz.de/lexikon/brodalumab-siliq 
ADVISORY COMMITTEE MEETING TOFACITINIB FOR THE TREATMENT OF RHEUMATOID ARTHRITIS im Jahr 2012 - http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ArthritisAdvisoryCommittee/UCM302960 http://rheumatologe.blogspot.de/2015/11/brodalumab-at-acr-2015-meeting-in-san.html 
http://rheumatologe.blogspot.de/2013/01/neue-therapien-bei-rheumatoider.html 
http://rheumatologe.blogspot.de/2016/08/protein-kinase-inhibitors-small.html

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